Bcl-xL sequesters its C-terminal membrane anchor in soluble, cytosolic homodimers

AUTOR(ES)

Jeong, Seon-Yong

RESUMO

Bcl-xL is a potent inhibitor of apoptosis. While Bcl-xL can be bound to mitochondria, a substantial fraction, depending on the cell type or tissue, is found in the cytosol of healthy cells. Gel filtration and crosslinking experiments reveal that, unlike monomeric Bax, Bcl-xL migrates in a complex of approximately 50 kDa in the cytosol. Co-immunoprecipitation experiments indicate that Bcl-xL in the cytosol forms homodimers. The C-terminal hydrophobic tails of two Bcl-xL molecules are involved in homodimer formation, and analysis of mutants demonstrates that the C-terminal lysine residue and the G138 residue lining the BH3-binding pocket are required for homodimerization. The flexible loop preceding the C-terminal tail in Bcl-xL is longer than that of several monomeric Bcl-2 family members and is a requisite for the homodimer formation. Bad binding to Bcl-xL dissociates the homodimers and triggers Bcl-xL binding to mitochondrial membranes. The C-terminal tail of Bcl-xL is also required to mediate Bcl-xL/Bax heterodimer formation. Both mitochondrial import and antiapoptotic activity of different Bcl-xL mutants correlate with their ability to form homodimers.

Documentos Relacionados

• Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis
• Modulation of cell death by Bcl-xL through caspase interaction
• Bcl-xL protects adult septal cholinergic neurons from axotomized cell death
• Human IAP-Like Protein Regulates Programmed Cell Death Downstream of Bcl-xL and Cytochrome c
• Receptor-mediated uptake of an extracellular Bcl-xL fusion protein inhibits apoptosis